ORIGINAL ARTICLE

Effect of intravenous methylprednisolone in

prevention of arterial hypoxemia due to fat
embolism syndrome in patients with long
bone fractures of lower limb - A double blind
randomized trial
Prashanth Nandibewur, Neeta Prashanth Nandibewur
Vijayanagara Institute of Medical Sciences (VIMS), Contonment, Ballari, Karnataka 583104, (India)

Correspondence: Dr Neeta P N, Assistant Professor, C- 128, 5th Main, 3rd Cross, Opposite Vishnuvardhan Park,
Kuvempnagar, Cantonment, Ballari- 583104 (India); Phone: 0-9844190501; E-mail: drnita10@gmail.com

ABSTRACT
Background: The fat embolism syndrome (FES) denotes clinical or subclinical respiratory insufficiency
developing in patients with long-bone fractures. It usually runs a mild course and responds well to measures
for respiratory support. The subclinical form is detected by blood gas analysis and is associated with a
PaO2 value of less than 60 mmHg. The present randomized double blind trial was conducted to evaluate
the effectiveness of intravenous corticosteroids in comparison with placebo for the prevention of arterial
hypoxemia in patients with long bone fractures.
Methodology: We conducted a double blinded randomized control trial among 44 patients, who showed
signs and symptoms of sub clinical fat embolism and fulfilled our inclusion and exclusion criteria over 2 years
period in a tertiary trauma care center. Forty four patients with long bone fractures were randomized as 20
patients in group A (control group) and 23 patients in group B (study group) respectively. The patients in the
experimental group received a single dose of 30 mg/kg intravenous methylprednisolone upon admission to
the emergency room. The control group received an equal volume of placebo (normal saline).
Results: The primary endpoints evaluated were the presence of fat embolism syndrome, based on the
Lindeques criteria. Arterial blood gas (ABG) analysis showed PO2 of 67 13 mmHg in Group A and 73
8 mmHg in Group B. Mean arterial oxygen was not significantly different between the two groups (P =
0.09), this shows that single dose methylprednisolone (30 mg/kg intravenously) is effective as prophylaxis for
prevention of arterial hypoxia in fat embolism syndrome. Among 44 patients studied 7 (33.33%) patients out
of 21 in Group A manifested clinical FES. In Group B, 2 (8.7%) out of 23 patients had manifestations of the
syndrome
Conclusion: Intravenous methylprednisolone administration to patients admitted with long-bone fractures
does not offer significant advantages in the maintenance of PaO2 and SPO2 levels when compared to placebo
(normal saline), but reduces the frequency of development of fat embolism syndrome.
Key words: Arterial blood gas; long bone fracture; methylprednisolone; fat embolism syndrome
Citation: Prashanth N, Neeta PN. Effect of intravenous methylprednisolone in prevention of arterial hypox-
emia due to fat embolism syndrome in patients with long bone fractures of lower limb - A double blind ran-
domized trial. Anaesth Pain & Intensive Care 2016;20(3):290-294
Received: 12 May 2016; Reviewed: 18 May & 10 June 2016; Accepted: 15 September 2016

INTRODUCTION Arterial blood gas analysis showing an unexplained

increase in pulmonary shunt fraction and an alveolar
Fat embolism syndrome (FES) is a respiratory
to arterial oxygen tension difference, especially
deficiency syndrome due to decreased alveolar
within 2448 h of a sentinel event associated with
diffusion of oxygen. It occurs in three degrees
FES, is strongly suggestive of the diagnosis. Blood
of severity: a subclinical, an overt clinical, and a
gases show hypoxia, with a PaO2 of less than 60
fulminating form. The subclinical fat embolism can
mmHg along with hypocapnia.2,3
be evaluated by peripheral oxygen saturation using
pulse oximeter and arterial blood gases analysis.1 Continuous pulse oximetry monitoring in high

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risk patients may help in detecting desaturation trauma. Institutional ethical clearance was obtained
early, allowing early institution of oxygen and and written informed consent was taken from all
possibly steroid therapy It would thus be possible the study subjects.
to decrease the chances of hypoxic insult and The patients were randomized to experimental and
systemic complications of FES.4 Preoperative use of control groups, the experimental group received
methylprednisolone may prevent the occurrence of a single intravenous dose of 30 mg/kg methyl-
FES.5 prednisolone over one hour in the emergency
Hypoxia is common after long bone fractures room, while the patients in the control group
and may pass unnoticed.2,7 There is no clinical received placebo, consisting of 50 ml intravenous
or experimental study until now to demonstrate normal saline over one hour. Randomization
beneficial effect of any drug on the clinical course was performed as follows: 50 envelopes were
of the syndrome,8 so that prevention, early prepared, with 25 as Group A (placebo group)
diagnosis and adequate symptomatic treatment and 25 as Group B (study group). On admission,
are the mainstays of treatment of this condition. patients who fulfilled the inclusion and exclusion
Several pharmacological agents have been used criteria were assigned randomly one envelope
as prophylactic treatment, such as hypertonic and segregated to respective group by the third
glucose,9 aspirin,5 dextrans5 and corticosteroids investigator (nursing staff) and administered
with variable results.1,9,10 the drug methylprednisolone or normal saline
accordingly. As a result, we got only 44 patients,
Rokkanen was the pioneer in utilizing steroid among these 21 in group A (placebo group) and
prophylactically in an attempt to reduce the 23 in group B (study group).The patients were
incidence of FES following massive trauma. This followed up by the principal investigator in the
was followed by the interesting piece of evidence ICU and on the wards. The group allocation was
provided by Kreis et al. who demonstrated that disclosed at the end of the study. Serial physical
corticosteroid improves oxygenation and decreases examinations and laboratory tests including arterial
the pathologic changes seen on pulmonary biopsies blood gas analyses were performed on admission
in experimental animals.11 and monitored sequentially (day 1 and day 2). All
The PaO2 reflects oxygen diffusion from the the patients underwent surgical fixation of bones
alveoli to the lung capillaries which is essential i.e. intramedullary nailing within 12 hours. FES was
for tissue oxygenation. For this reason we used diagnosed based on the Lindeques criteria.1
the PaO2 values to compare the effectiveness of 1. A sustained PaO2 of less than 8 kPa (60 mmHg)
methylprednisolone against a placebo. Owing with FiO2 0.21.
to the subjective and variable nature of clinical 2. A sustained PaCo2 of more than 7.3 kPa (55
diagnostic criteria, we mainly assessed objective mmHg) or pH of less than 7.3
findings suggestive of FES, including the presence 3. A sustained respiratory rate of greater than 35
of hypoxia. Accordingly, the present study breath/min. even after adequate sedation.
evaluated the effectiveness of methylprednisolone 4. Increased work of breathing as judged by
in the prevention of development of FES, arterial dyspnea, use of accessory muscles, tachycardia
hypoxia, in patients with long bone fracture(s). and anxiety.
Any patient with fracture femur and/or tibia
METHODOLOGY showing one or more of these criteria was judged
A randomized double blind placebo-controlled as having FES.
trial was performed on 44 patients with long bone Data were analyzed and expressed in terms of rates,
fractures, who showed symptoms suggestive of ratios and percentages. The statistical evaluation
subclinical FES, over a period of one year May was accomplished using the unpaired t-test. A p <
2009 to May 2010, in a tertiary care hospital. The 0.05 was considered significant.
study included patients between of 16 and 46 years
presented to our emergency room during the first RESULTS
24 hours of the fracture. Patients were excluded
if they had following systemic or chronic disease; Forty four patients completed the study. Of these,
pathologic fracture, pregnancy, previous steroid 37 patients had fracture femur (84.1 %) while seven
treatment, fractures with compartment syndrome, patients had fracture tibia (15.9 %).
or they had accompanied head, chest, or abdominal In the experimental group, two patients developed

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methylprednisolone to prevent hypoxemia in fat embolism syndrome

Table 1: Arterial blood gas analysis of patients in two groups on admission, day 1 and day 2
Group A Group B
Arterial Blood Gases t Statistic P value
Mean SD Mean SD
PO2 on Admission 60.81 4.93 63.3 4.54 -1.73 0.9
PO2 on Day 1 62.76 5.71 64.87 5.99 -1.19 0.24
PO2 on Day 2 66.81 13.07 73.48 8.51 -1.98 0.05
PCO2 on Admission 34.57 4.56 33.43 5.63 0.73 0.46
PCO2 on Day 1 35.62 3.62 33.57 3.97 1.79 0.08
PCO2 on Day 2 35.9 4.23 34.7 2.6 1.12 0.27
PH on Admission 7.32 0.05 7.33 0.05 -1.39 0.2
PH on Day 1 7.33 0.03 7.34 0.03 -1.48 0.15
PH on Day 2 7.33 0.04 7.35 0.23 -1.67 0.11

FES (8.7%), whereas in the control group, seven

patients developed the syndrome (33.33%). Mean
age of Group A patients was 26.95 years and 28.78
years for Group B. Majority of patients (76.19%
Group A & 86.96% Group B) were males.
On admission, the mean PO2 in B was 63.30
4.55 mmHg (range: 53.0-71.0 mmHg) and 60.81
4.93 mmHg (range: 51.0-70.0 mmHg) in control
group. Statistical analysis revealed that there is no
significant difference in the number of patients
with arterial hypoxemia or mean arterial oxygen
pressure, PCO2 and PH values. (Table 1)
Figure 1: Shows the trend in PO2 in patients of two groups
The arterial blood gas analysis showed a PO2 of 61
mmHg and 63 mmHg and PCO2 of 34 mmHg and
33 mmHg on admission in Group A and Group B
respectively. Post operatively arterial blood gases
(ABG) shows a PO2 of 67 13 mmHg in Group A
73 8 mmHg in Group B. PCO2 did not show a
variation in two groups (Figure 1).
In the experimental group, all 23 patients had an
initial baseline Pa02 value of more than 53 mmHg;
in two of them, this fell to below 55 mmHg on
day one and in two on day 2 during the trial. In
the control group, 20 patients had baseline PO2
of more than 55 mmHg; in two of them, PO2 fell
Figure 2: Shows the trend in PCO2 in patients of two groups
below 55 mmHg during day 1 and in seven patients
below 55 mmHg on day 2. This difference was not
statistically significant (Figure 1).
Arterial blood gas analysis on admission showed
mean PO2 of 60.81 mmHg in Group A and 63.3
mmHg in Group B: the mean PCO2 levels were 34.57
mmHg and 33.43 mmHg; and the pH was 7.32 and
7.33 in the two groups respectively (Figure 2).
Among 44 patients studied 7 (33.33%) patients out
of 21 in Group A manifested clinical FES. In Group
B, 2 (8.7%) out of 23 patients had manifestation of Figure 3: Comparison of the incidence of clinical FES in two
groups of patients
syndrome (Figure 3).

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DISCUSSION oxygen pressure.

Hypoxemia is one of the important signs of fat One study stated that methylprednisolone
FES. Tachakra et al6 studied relation between succinate, in a single dose of 10 mg/kg, was not
hypoxia and fractures of femur and tibia. They effective in prevention of FES, although it decreased
studied fifty patients with fractures of lower limb its incidence. Corticosteroid therapy has been
and pelvis. Arterial blood gas analysis showed a recommended in selected cases in patients with
phase of hypoxia in 32 out of 50 fracture patients multiple or bilateral long bone fractures.13 We used
without head, chest or abdominal injury. The PO2 a higher dose of 30 mg/kg of methylprednisolone
in this hypoxemia was between 60 to 70 mmHg. He prophylactically in anticipation of better effect than
the lower dose used by earlier investigators. May
concluded that pulmonary fat embolism is the most
be because of that our results were more favorable
likely explanation of the hypoxemic episodes.
in preventing FES as well as maintaining arterial
The treatment of FES is difficult due to lack blood gas levels.
of specific diagnostic indicators. Symptomatic
The incidence of clinical FES in study group
treatments such as protecting critical tissues and
patients (8.7%) was significantly lower (chi square
organs (such as the lungs and brain), correcting test, p-value= 0.0430) than that in control group
hypoxemia, respiratory support, and prevention of patients (33.3%). Our study demonstrated that
complications were performed as major therapeutic methylprednisolone 30 mg/kg significantly reduces
measures, death and disability remain major threats the incidence of FES when given as a single
to these patients.12,13 Prevention is essential and prophylactic dose. This is in close agreement to
improves the success rate of treatment and reduces the study by Antti Alho and colleagues17 where
the rate of disability.14,15 methylprednisolone 30 mg/kg was given in divided
The Arterial Blood Gas (ABG) values on room air doses.
in these patients showed mean values of PO2 61
mmHg, PCO2 33 mmHg and pH 7.32. The PO2 CONCLUSION
values were similar to that obtained by Tachakra
In summary, use of methylprednisolone 30 mg/kg
et al6. This overall picture of hypoxemia following
did not show statistically significant improvement
long bone fracture was suggestive of fat embolism.
in the arterial blood gas values, but the incidence
Another study showed much higher PO2 levels.13
of fat embolism syndrome was reduced in this
Collins14 reported that arterial PO2 fell below 80 group than in the placebo group. The routine early
mmHg in one third of 33 patients with comminuted administration of intravenous methylprednisolone
femoral shaft fractures. Bradford et al15 found to patients admitted with long bone fractures offers
arterial oxygen saturation below 90 % in eight out an advantage in the maintenance of PaO2 and SPO2
of 23 patients in one or more fractures of tibia and levels and a reduction in the incidence of the FES.
femur. McCarthy et al16 observed a fall in PaO2 below
80 mmHg during first two days after injury in 28 Acknowledgement: We thank our hospital staff members and
out of 50 patients with fractures of the extremities patients for participating in our study.
.In our study we found no significant difference Conflicts of interest: None declared.
between the two groups with regard to number of Authors contribution: Both authors took equal part in the concept,
patients with arterial hypoxemia or mean arterial conduct of the study nd the manuscript preparation.

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methylprednisolone to prevent hypoxemia in fat embolism syndrome

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